Hematological disorders are blood associated disorders. Blood is a highly specialized tissue which carries oxygen and nutrients to all parts of the body and waste products back to the lungs, kidneys and liver for disposal. Thus, blood maintains communication between different parts of the body. Blood is also an essential part of the immune system, crucial to fluid and temperature balance, a hydraulic fluid for certain functions and a highway for hormonal messages.
All blood cells in adults are produced in the bone marrow. Red cells, white cells and platelets are produced in the marrow of bones, especially the vertebrae, ribs, hips, skull and sternum. These essential blood cells fight infection, carry oxygen and help control bleeding. Specifically, red blood cells are disc-shaped cells containing hemoglobin, which enables these cells to pick up and deliver oxygen to all parts of the body. White blood cells are the body's primary defense against infection. They can move out of the blood stream and reach tissues being invaded. Platelets are small blood cells that control bleeding by forming clusters to plug small holes in blood vessels and assist in the clotting process.
Each day the bone marrow generates and releases into the circulation several billion fully-differentiated, functional blood cells. Hematopoiesis is the process by which blood cells develop and differentiate from pluripotent stem cells in the bone marrow. Production of these cells derives from a small stock of quiescent progenitor cells (including the most primitive stem cells and other less primitive but still immature progenitors). The most primitive stem cells have the capacity to generate several billion cells containing all blood lineages. The production of such a large number of cells is achieved by extensive proliferation coupled with successive differentiation steps leading to a balanced production of mature cells.
The production of mature blood cells by the hematopoietic system involves complex interactions between soluble factors, the marrow microenvironment, and hematopoietic progenitors. In particular, hematopoiesis involves a complex interplay of polypeptide growth factors acting via membrane-bound receptors on their target cells. Signaling by growth factors results in cellular proliferation and differentiation, with a response to a particular growth factor often being lineage-specific and/or stage-specific. Development of a single cell type, such as a red blood cell, from a stem cell may require the coordinated action of a plurality of growth factors acting in the proper sequence.
Impaired blood cell production occurs when the proliferation and differentiation of the stem cells or committed cells is disturbed. Impaired blood cell production is the root of hematological disorders. Some of the more common diseases caused by impaired blood cell production, i.e., hematological disorders, include aplastic anemia, hypoplastic anemia, pure red cell aplasia and anemia associated with renal failure or endocrine disorders. Disturbances in the proliferation and differentiation of erythroblasts include defects in DNA synthesis such as impaired utilization of vitamin B12 or folic acid and the megaloblastic anemias, defects in heme or globin synthesis, and anemias of unknown origins such as sideroblastic anemia, anemia associated with chronic infections such as malaria, trypanosomiasis, HIV, hepatitis virus or other viruses, and myelophthisic anemias caused by marrow deficiencies. Impaired blood cell production also affects cancer patients and other autoimmune disease patients who receive bone marrow irradiation or chemotherapy treatment.
Hematological disorders are, thus, a diverse family of disorders embracing clinical and laboratory aspects of a large number of diseases, both malignant and non-malignant. Although some progress has been made in diagnostic and therapeutic strategies to combat hematological disorders, molecular advances are continuing at a rate exceeding the rate of progress in therapeutics. Thus, novel methods for diagnosis and treatment of hematological disorders based on known molecular advances are urgently needed in the field.